Comparison of the Risk of Cancer Between Patients With Type 2 Diabetes Exposed to Dapagliflozin and Those Exposed to Other Antidiabetic Treatments

Study type

• Study topic:
  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  FORXIGA

  XIGDUO
• Name of medicine, other:
  Farxiga, Xigduo XR
• Study drug International non-proprietary name (INN) or common name:
  DAPAGLIFLOZIN
• Anatomical Therapeutic Chemical (ATC) code:
  (A10BD15) metformin and dapagliflozin

  metformin and dapagliflozin

  (A10BD21) saxagliptin and dapagliflozin

  saxagliptin and dapagliflozin

  (A10BD25) metformin, saxagliptin and dapagliflozin

  metformin, saxagliptin and dapagliflozin

  (A10BK01) dapagliflozin

  dapagliflozin
• Medical condition to be studied:
  Breast cancer

  Bladder cancer

Population studied

• Short description of the study population:
  Patients newly initiating dapagliflozin (with or without concomitant use of any other antidiabetic drugs [AD]) or newly initiating an eligible comparator AD (with or without concomitant use of any other AD) during the study period, evaluated for selection into the study cohorts individually for study from each data source.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  1800000

Study design details

• Study design:
  Cohort study with an active-comparator, new-user design.
• Main study objective:
  To compare, among patients with type 2 diabetes, who are new users of dapagliflozin and patients who are new users of ADs (1) the incidence of invasive breast cancer and (2) the incidence of in situ and invasive bladder cancer.
• Setting:
  The study is being conducted in four population-based health care data sources:; • CPRD in the UK, specifically, CPRD GOLD; • PHARMO in the Netherlands; • The HIRD in the US; • Medicare in the US;
• Comparators:
  New users of ADs in classes other than SGLT2 inhibitors, insulin monotherapy, metformin monotherapy, or sulfonylurea monotherapy.
• Outcomes:
  Primary outcomes: Female breast cancer and bladder cancer.; Secondary outcomes: Composite incidence of selected cancers among males (prostate, colon/rectum, lung, stomach, non-Hodgkin lymphoma (NHL), and melanoma of skin) and among females (colon/rectum, lung, corpus uteri, ovary, stomach, NHL and melanoma of skin). Frequency of health care utilization measures during follow up.
• Data analysis plan:
  Descriptive statistics will be calculated to compare baseline characteristics at cohort entry between dapagliflozin users versus comparator antidiabetic users separately for each outcome. ; Propensity scores will be estimated by using logistic regression, with measured potential predictors of the cancer outcome as independent variables in the regression model and actual exposure group (dapagliflozin or comparator) as the outcome. ; Incidence rates of each outcome will be estimated during exposure time at risk for dapagliflozin initiators and comparators. ; Unadjusted incidence rate ratios (IRRs) of the outcomes of interest with 95% confidence intervals in dapagliflozin users versus other AD users will be calculated and adjusted using propensity score–stratified analysis. ; Analyses will be conducted in each data source separately, and a pooled estimate will be calculated if deemed appropriate.